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Renin enhancer knockout mice have lower blood pressure and locomotor activity but normal baroreflexes
Author(s) -
Head Geoffrey A,
Mayorov Dmitry N,
LaGreca Luisa,
Jackson Kristy,
Adams David J,
Lovicu Frank J,
Markus Andrea M,
Morris Brian J
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1405-c
The promoter that controls renin expression is under the strong influence of a far (2.6 kb)‐upstream enhancer. Mice have been generated with targeted deletion of the Ren‐1c enhancer (REKO mice) and which show low expression of renin. We compared cardiovascular variables in REKO and wild‐type (WT) mice to determine the importance of the renin gene enhancer in blood pressure regulation. Male C57BL6 (WT) and renin‐enhancer knockout (REKO) mice (n=8) were implanted with telemetry devices to monitor mean arterial pressure (MAP), heart rate (HR), and locomotor activity in the unrestrained state. Mice were placed on high (3.1%), normal (0.4%) and low (0.05%) NaCl for a period of 2 weeks and the diet rotated for a total of 6 weeks of the study. The average 24 hour MAP was 114 mmHg for WT and 104 mmHg for REKO mice on the normal salt diet (P<0.001). HR was similar in the 2 groups, but locomotor activity was 41% lower in the REKO mice (P<0.001). Day‐night differences in MAP and HR were also similar in the 2 strains. A 3% high salt diet normalized MAP in the REKO mice, but had no effect in the WT mice. Blood pressure and HR variability, HR baroreflex sensitivity assessed by spectral analysis were similar. The renin enhancer is necessary to maintain blood pressure and also to prevent hypertensive responses to a high salt diet but is not important for cardiac baroreflexes, or short term and diurnal BP variability. The reduction in locomotor activity suggests a role for the renin enhancer and renin in CNS regulation of locomotor activity.